Calcium/calcimimetic via calcium-sensing receptor ameliorates cholera toxin-induced secretory diarrhea in mice

Figure 4 Diagram illustrates how cholera toxin stimulates and calcium/calcimimetic inhibits the dual pathways of Cl^- secretion resulting in diarrhea. Cholera toxin (CTX) via G_s α-subunit stimulates transepithelial Cl^- secretion both neurally through Nestin-expressing enteric neurons releasing neurotransmitters and non-neuronally through direct action on Villin-expressing epithelial cells. The outcome is stimulating both Cl^- entry from blood side into intestinal epithelial cell and exit from epithelial cell into the intestinal lumen causing secretory diarrhea. On the other hand, Ca²⁺/calcimimetic via calcium-sensing receptor (CaSR) inhibits both actions of CTX via direct epithelial action and indirectly via enteric neuron. The involvement of Nestin-expressing enteric neurons and Villin-expressing epithelial cells is evidenced in the two tissue-specific knockout mice whose Cl^- secretory responses to CTX and CaSR stimulation are compromised.